Frog deformities research not leaping to conclusions.

Che-1 is a RNA polymerase II binding protein involved in the transcriptional regulation of E2F target genes and in cell proliferation. Recently, it has been shown that Che-1 accumulates in cells responding to genotoxic agents such as Doxorubicin and ionizing radiation. The DNA damageactivated checkpoint kinases ATM and Chk2 interact with and phosphorylate Che-1, enhancing its accumulation and stability, and promoting Che-1-mediated transcription of p53-responsive genes and of p53 itself, as evidenced by microarray analysis. This transcriptional response is suppressed by expression of a Che-1 mutant lacking ATM and Chk2 phosphorylation amino acid residues, or by depletion of Che-1 by RNA silencing. In addition, chromatin immunoprecipitation analysis has shown that Che-1 is released from E2F target genes and recruited to the p21 and p53 promoters after DNA damage. Che-1 contributes to the maintenance of the G2/M checkpoint in response to genotoxic stress. These findings identify a new mechanism by which the checkpoint kinases regulate, via the novel effector Che-1, the p53 pathway. Lastly, increasing evidence suggests that Che-1 may be involved in apoptotic signaling in neural tissues. In cortical neurons, Che-1 exhibits anti-apoptotic activity, protecting cells from neuronal damage induced by amyloid β-peptide. In cerebellar granule neurons, Che-1 interacts with Tau in the cytoplasmic compartment and this interaction is modulated during neuronal apoptosis. Finally, Che-1 directly interacts with the neuronal cell-death inducer "NRAGE" which downregulates endogenous Che-1 by targeting it for proteasome-dependent degradation. These findings identify Che-1 as a novel cytoprotective factor against apoptotic insults and suggest that Che-1 may represent a potential target for therapeutic application. Background Che-1, also called AATF or Ded, is a phosphoprotein containing 558 amino acids and has been identified as a RNA polymerase II binding protein in a two-hybrid screen [1]. Human Che-1 was also cloned by differential display of genes downregulated by TGFβ [2]. The human Che-1 gene is located at chromosome 17q11.2-q12, and Che-1 is highly conserved among eukaryotic species [2]. Che-1 expression is essential during the early steps of embryogenesis. Indeed, in the absence of a fully functional Traube gene (the murine ortholog of Che-1), embryos halt in development at the compacted morula stage and die 2 days later [3]. Published: 16 July 2007 Cell Division 2007, 2:21 doi:10.1186/1747-1028-2-21 Received: 5 June 2007 Accepted: 16 July 2007 This article is available from: http://www.celldiv.com/content/2/1/21 © 2007 Passananti and Fanciulli; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.